α-突触核蛋白转基因帕金森病模型小鼠早期出现社交认知障碍  

α-Synuclein transgenic mouse model of Parkinson disease exhibits social cognition impairment in early stage

作　　者：任湘鹏 侯志东[2] 田静 徐煌 王琰萍[3] REN Xiang-peng;HOU Zhi-dong;TIAN Jing;XU Huang;WANG Yan-ping(College of Medicine,Jiaxing University,Jiaxing 314001,China;School of Ophthalmology and Optometry,Wenzhou Medical University,Wenzhou 325027,China;Department of Neurology,The Second Affiliated Hospital,Jiaxing University,Jiaxing 314001,China)

机构地区：[1]嘉兴学院医学院,浙江嘉兴314001 [2]温州医科大学眼视光学院,浙江温州325027 [3]嘉兴学院附属第二医院神经内科,浙江嘉兴314001

出　　处：《中国病理生理杂志》2022年第7期1169-1176,共8页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金资助项目(No.LY18H090012);嘉兴市科技局公益性研究计划项目(No.2021AY10048);嘉兴学院科研启动项目(No.CD70520032)。

摘　　要：目的:探讨α-突触核蛋白(αS)转基因(TG)帕金森病(PD)模型小鼠早期的非运动行为及相关病理改变。方法:以6月龄A53T突变型αS(A53TαS)TG小鼠作为早期PD小鼠模型,通过旷场实验、悬挂实验及精细运动实验评估PD模型小鼠的运动能力;通过Y迷宫自发交替行为实验、高架十字迷宫、悬尾实验和三箱社交实验分别评价PD模型小鼠的工作记忆、焦虑、抑郁样情绪及社交认知能力等非运动行为学表型;通过免疫组化检测PD模型小鼠脑内黑质区多巴胺(DA)能神经元及皮层区αS病理性包涵体;通过Western blot检测PD模型小鼠脑内黑质区酪氨酸羟化酶(TH)及皮层区Polo样激酶2(PLK2)的表达水平。结果:行为学实验结果显示,A53TαS TG PD模型小鼠的总移动距离、悬挂时间、磕瓜子数目、自发转换正确率、开放臂停留时间及肢体静止不动时间均未发生显著改变,但在三箱社交实验第3时相中与新目标鼠的交流时间显著减少(P<0.01)。免疫组化及Western blot结果显示,A53TαS TG PD模型小鼠脑内黑质区DA能神经元及TH表达水平未出现显著改变,但皮层区出现αS病理性包涵体及PLK2表达水平上调(P<0.01)。结论:A53TαS TG PD模型小鼠早期未出现运动、工作记忆及情绪样行为异常,但表现出社交认知障碍,可能与皮层中αS病理性包涵体相关。AIM:To observe the non-motor behavior and related pathological changes inα-synuclein(αS transgenic(TG)mice.METHODS:Six-month-old A53T mutantαS(A53TαS)TG mice were used as mouse model for early Parkinson disease(PD).Motor behavior of the PD mice was evaluated by open-field test,wire hang test and fine movement test.Non-motor behavior such as working memory,anxiety,depression-like emotions and social cognitive ability of the PD mice were evaluated by Y-maze spontaneous alternation behavior(SAB)test,elevated plus maze,tail suspension test and three-chambered social approach task,respectively.Dopaminergic(DA)neurons in substantia nigra andαS pathological inclusions in cortex of the PD mice were detected by immunohistochemical staining.The expression levels of tyrosine hydroxylase(TH)in substantia nigra and Polo-like kinase 2(PLK2)in cortex of the PD mice were determined by Western blot.RESULTS:No difference in total moving distance,hanging time,fine movement,SAB accuracy,time in open arm and immobility time were observed between control and A53TαS TG PD mice.However,A53TαS mice spent less time communicating with new target mice in phase 3 during the three-chambered social task(P<0.01).The DA neurons and the expression of TH in the substantia nigra were not changed,whileαS pathological inclusions were observed and the expression of PLK2 was up-regulated in the cortex of the PD mice(P<0.01).CONCLUSION:Social cognition impairment is related toαS pathological inclusions in the cortex of A53TαS TG PD mice.

关 键 词：帕金森病 Α-突触核蛋白 转基因小鼠模型 社交认知障碍 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R363.2[医药卫生—临床医学]